Despite the growing body of evidence to support Kaposi=s sarcoma-associated herpesvirus (KSHV) as the etiological agent in many AIDS and non-AIDS-related malignancies, understanding how KSHV is involved in these malignancies is important for the generation of therapies against the spectrum of KSHV-associated diseases. Last year we reported that SIV-infected rhesus macaques experimentally infected with the rhesus HHV8 homologue, now referred to as rhesus rhadinovirus (RRV), developed B cell hyperplasia and persistent lymphadenopathy that resembled multicentric Castleman=s disease. This past year, we made the following observations from in vitro and in vivo experiments. 1) Sequence and genomic analysis of the RRV genome reveals that it is closely related to KSHV/HHV8, as it is essentially co-linear with and encodes several of the unique cellular homologues that are found in the KSHV genome. 2) Experimental inoculation of SIV-infected rhesus macaques with RRV strai n 17577 confirms our pilot studies, that RRV-infection of SIV-infected macaques results in the induction of B cell hyperplasia and persistent lymphadenopathy. 3) Expression of the RRV IL-6-like cytokine gene, in either COS-1-transfected cells or as a Glutathione S-transferase fusion protein in E. coli, possesses IL-6-like activity when measured by bioassay using IL-6-dependent cell lines. Combined, these studies support our initial hypothesis that this virus can cause disease manifestations in SIV-infected rhesus macaques that resemble some of those manifested in AIDS patients with Kaposi=s sarcoma. FUNDING NIH CA75922 PUBLICATIONS Kaleeba JAR, Bergquam E, Swanson R, Searles RP, Wong SW. Characterization of gene expression by a rhesus gamma-2 herpesvirus related to Kaposi=s sarcoma-associated herpesvirus. In Kaposi=s Sarcoma-Associated Herpesvirus (KSHV) and Related Agents Program & Abstracts 1st Annual Meeting (held in Santa Cruz, CA, July 25-28, 1998) (abstract 31). Kaleeba JAR, Bergquam EP, Wong SW. A strain of rhesus rhadinovirus (RRV 17577) related to Kaposi=s sarcoma-associated herpesvirus encodes a functional homologue of cellular interleukin 6. In 16th Annual Symposium on Nonhuman Primate Models for AIDS (held in Atlanta, GA, October 7-10, 1998) (abstract 32). Searles, RP, Bergquam EP, Axthelm MK, Wong SW. Characterization of a rhesus macaque gamma-2 herpesvirus with homology to Kaposi=s sarcoma-associated herpesvirus (KSHV). In Kaposi=s Sarcoma-Associated Herpesvirus and Related Agents Program & Abstracts 1st Annual Meeting (held in Santa Cruz, CA, July 25-28, 1998) (abstract 29). Wong SW, Bergquam EP, Swanson R, Shiigi S, Axthelm MK. A rhesus gamma-2 herpesvirus related to Kaposi=s sarcoma-associated herpesvirus is associated with B cell abnormalities in SIV-infected rhesus macaques. In Kaposi=s Sarcoma-associated Herpesvirus and Related Agents Program & Abstracts 1st Annual Meeting (held in Santa Cruz, CA, July 25-28, 1998) (abstract 30).